scholarly journals Having an Old Friend for Dinner: The Interplay between Apoptotic Cells and Efferocytes

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1265
Author(s):  
Austin Le Lam ◽  
Bryan Heit
Keyword(s):  
Complete Removal ◽  
Surrounding Tissue ◽  
Apoptotic Cells ◽  
Negative Consequences ◽  
Secondary Necrosis ◽  
Cellular Processes ◽  
End Point ◽  
Multicellular Organisms

Apoptosis, the programmed and intentional death of senescent, damaged, or otherwise superfluous cells, is the natural end-point for most cells within multicellular organisms. Apoptotic cells are not inherently damaging, but if left unattended, they can lyse through secondary necrosis. The resulting release of intracellular contents drives inflammation in the surrounding tissue and can lead to autoimmunity. These negative consequences of secondary necrosis are avoided by efferocytosis—the phagocytic clearance of apoptotic cells. Efferocytosis is a product of both apoptotic cells and efferocyte mechanisms, which cooperate to ensure the rapid and complete removal of apoptotic cells. Herein, we review the processes used by apoptotic cells to ensure their timely removal, and the receptors, signaling, and cellular processes used by efferocytes for efferocytosis, with a focus on the receptors and signaling driving this process.

scholarly journals Having an Old Friend For Dinner: The Interplay between Apoptotic Cells and Efferocytes

2021 ◽  
Author(s):  
Austin Le Lam ◽  
Bryan Heit
Keyword(s):  
Apoptotic Cell ◽  
Complete Removal ◽  
Surrounding Tissue ◽  
Apoptotic Cells ◽  
Negative Consequences ◽  
Secondary Necrosis ◽  
Cellular Processes ◽  
End Point ◽  
Multicellular Organisms

Apoptosis, the programmed and intentional death of senescent, damaged, or otherwise superfluous cells, is the natural end-point for most cells within multicellular organisms. Apoptotic cells are not inherently damaging, but if left unattended they can lyse through secondary necrosis. The resulting release of intracellular contents drives inflammation in the surrounding tissue and can lead to autoimmunity. These negative consequences of secondary necrosis are avoided by efferocytosis—the phagocytic clearance of apoptotic cells. Efferocytosis is a product of both apoptotic cell and efferocyte mechanisms, which cooperate to ensure the rapid and complete removal of apoptotic cells. Herein, the processes used by apoptotic cells to ensure their timely removal, and the receptors, signaling, and cellular processes used by efferocytes to identify, remove, and process the apoptotic cells, are reviewed.

scholarly journals Development of Inflammatory Angiogenesis by Local Stimulation of Fas In Vivo

1997 ◽  
Vol 186 (1) ◽  
pp. 147-152 ◽  
Author(s):  
Luigi Biancone ◽  
Antonella De Martino ◽  
Viviana Orlandi ◽  
Pier Giulio Conaldi ◽  
Antonio Toniolo ◽  
...  
Keyword(s):  
Fas Ligand ◽  
Surrounding Tissue ◽  
Apoptotic Cells ◽  
Lymphocyte Apoptosis ◽  
Ligand Interaction ◽  
Monocytes And Macrophages ◽  
Inflammatory Angiogenesis ◽  
Local Stimulation ◽  
Stimulation Of

Fas–Fas ligand interaction is thought to be a crucial mechanism in controlling lymphocyte expansion by inducing lymphocyte apoptosis. However, Fas is also broadly expressed on nonlymphoid cells, where its function in vivo remains to be determined. In this study, we describe the development of inflammatory angiogenesis induced by agonistic anti-Fas mAb Jo2 in a murine model where Matrigel is used as a vehicle for the delivery of mediators. The subcutaneous implants in mice of Matrigel containing mAb Jo2 became rapidly infiltrated by endothelial cells and by scattered monocytes and macrophages. After formation and canalization of new vessels, marked intravascular accumulation and extravasation of neutrophils were observed. Several mast cells were also detected in the inflammatory infiltrate. The phenomenon was dose and time dependent and required the presence of heparin. The dependency on activation of Fas is suggested by the observation that the inflammatory angiogenesis was restricted to the agonistic anti-Fas mAb and it was absent in lpr Fas-mutant mice. Apoptotic cells were not detectable at any time inside the implant or in the surrounding tissue, suggesting that angiogenesis and cell infiltration did not result from recruitment of phagocytes by apoptotic cells but rather by a stimulatory signal through Fas-engagement. These findings suggest a role for Fas–Fas ligand interaction in promoting local angiogenesis and inflammation.

Apoptotic cells subjected to cold/warming exposure disorganize apoptotic microtubule network and undergo secondary necrosis

APOPTOSIS ◽  
2014 ◽  
Vol 19 (9) ◽  
pp. 1364-1377 ◽  
Author(s):  
Manuel Oropesa-Ávila ◽  
Alejandro Fernández-Vega ◽  
Mario de la Mata ◽  
Juan Garrido-Maraver ◽  
David Cotán ◽  
...  
Keyword(s):  
Apoptotic Cells ◽  
Microtubule Network ◽  
Secondary Necrosis

Role of macrophage CD44 in the disposal of inflammatory cell corpses*

2002 ◽  
Vol 103 (5) ◽  
pp. 441-449 ◽  
Author(s):  
Sharon VIVERS ◽  
Ian DRANSFIELD ◽  
Simon P. HART
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Surrounding Tissue ◽  
Human Macrophage ◽  
Neutrophil Granulocytes ◽  
Apoptotic Cells ◽  
Tissue Destruction

Understanding the cellular and molecular mechanisms that determine whether inflammation resolves or progresses to scarring and tissue destruction should lead to the development of effective therapeutic strategies for inflammatory diseases. Apoptosis of neutrophil granulocytes is an important determinant of the resolution of inflammation, providing a mechanism for down-regulation of function and triggering clearance by macrophages without inducing a pro-inflammatory response. However, if the rate of cell death by apoptosis is such that the macrophage clearance capacity is exceeded, apoptotic cells may progress to secondary necrosis, resulting in the release of harmful cellular contents and in damage to the surrounding tissue. There are many possible ways in which the rate and capacity of the macrophage-mediated clearance of apoptotic cells may be enhanced or suppressed. Ligation of human macrophage surface CD44 by bivalent monoclonal antibodies rapidly and profoundly augments the capacity of macrophages to phagocytose apoptotic neutrophils in vitro. The molecular mechanism behind this effect and its potential significance in vivo is a current focus of research.

scholarly journals Minimally invasive removal of lumbar intradural extramedullary lesions using the interlaminar approach

2015 ◽  
Vol 39 (2) ◽  
pp. E10 ◽  
Author(s):  
Yong-Jian Zhu ◽  
Guang-Yu Ying ◽  
Ai-Qin Chen ◽  
Lin-Lin Wang ◽  
Dan-Feng Yu ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Bone Destruction ◽  
Length Of Hospital Stay ◽  
Complete Removal ◽  
Tumor Location ◽  
Surrounding Tissue ◽  
Spinal Instability ◽  
Interlaminar Approach ◽  
Intradural Extramedullary

OBJECT Posterior midline laminectomy or hemilaminectomy has been successfully applied as the standard microsurgical technique for the treatment of spinal intradural pathologies. However, the associated risks of postoperative spinal instability increase the need for subsequent fusion surgery to prevent potential long-term spinal deformity. Continuous efforts have been made to minimize injuries to the surrounding tissue resulting from surgical manipulations. The authors report here their experiences with a novel minimally invasive surgical approach, namely the interlaminar approach, for the treatment of lumbar intraspinal tumors. METHODS A retrospective review was conducted of patients at the Second Affiliated Hospital of Zhejiang University School of Medicine who underwent minimally invasive resection of lumbar intradural-extramedullary tumors. By using an operative microscope, in addition to an endoscope when necessary, the authors were able to treat all patients with a unilateral, paramedian, bone-sparing interlaminar technique. Data including preoperative neurological status, tumor location, size, pathological diagnosis, extension of resections, intraoperative blood loss, length of hospital stay, and clinical outcomes were obtained through clinical and radiological examinations. RESULTS Eighteen patients diagnosed with lumbar intradural-extramedullary tumors were treated from October 2013 to March 2015 by this interlaminar technique. A microscope was used in 15 cases, and the remaining 3 cases were treated using a microscope as well as an endoscope. There were 14 schwannomas, 2 ependymomas, 1 epidermoid cyst, and 1 enterogenous cyst. Postoperative radiological follow-up revealed complete removal of all the lesions and no signs of bone defects in the lamina. At clinical follow-up, 14 of the 18 patients had less pain, and patients' motor/sensory functions improved or remained normal in all cases except 1. CONClUSIONS When meeting certain selection criteria, intradural-extramedullary lumbar tumors, especially schwannomas, can be completely and safely resected through a less-invasive interlaminar approach using a microscope, or a microscope in addition to an endoscope when necessary. This approach was advantageous because it caused even less bone destruction, resulting in better postoperative spinal stability, no need for facetectomy and fusion, and quicker functional recovery for the patients. Individualized surgical planning according to preoperative radiological findings is key to a successful microsurgical resection of these lesions through the interlaminar space.

scholarly journals Caspase Activity Is Required for Engulfment of Apoptotic Cells

2013 ◽  
Vol 33 (16) ◽  
pp. 3191-3201 ◽  
Author(s):  
Boris Shklyar ◽  
Flonia Levy-Adam ◽  
Ketty Mishnaevski ◽  
Estee Kurant
Keyword(s):  
Central Nervous System ◽  
Normal Development ◽  
Function Analysis ◽  
Living Cells ◽  
Apoptotic Cells ◽  
Caspase Activity ◽  
Internal Inhibition ◽  
Content Type ◽  
Multicellular Organisms ◽  
Dying Cells

Clearance of apoptotic cells by phagocytic neighbors is crucial for normal development of multicellular organisms. However, how phagocytes discriminate between healthy and dying cells remains poorly understood. We focus on glial phagocytosis of apoptotic neurons during development of theDrosophilacentral nervous system. We identified phosphatidylserine (PS) as a ligand on apoptotic cells for the phagocytic receptor Six Microns Under (SIMU) and report that PS alone is not sufficient for engulfment. Our data reveal that, additionally to PS exposure, caspase activity is required for clearance of apoptotic cells by phagocytes. Here we demonstrate that SIMU recognizes and binds PS on apoptotic cells through its N-terminal EMILIN (EMI), Nimrod 1 (NIM1), and NIM2 repeats, whereas the C-terminal NIM3 and NIM4 repeats control SIMU affinity to PS. Based on the structure-function analysis of SIMU, we discovered a novel mechanism of internal inhibition responsible for differential affinities of SIMU to its ligand which might prevent elimination of living cells exposing PS on their surfaces.

scholarly journals Loss of GET pathway orthologs inArabidopsis thalianacauses root hair growth defects and affects SNARE abundance

2017 ◽  
Vol 114 (8) ◽  
pp. E1544-E1553 ◽  
Author(s):  
Shuping Xing ◽  
Dietmar Gerald Mehlhorn ◽  
Niklas Wallmeroth ◽  
Lisa Yasmin Asseck ◽  
Ritwika Kar ◽  
...  
Keyword(s):  
Root Hair ◽  
Yeast Cells ◽  
Hydrophobic Domain ◽  
Protein Insertion ◽  
Cellular Processes ◽  
Growth Defects ◽  
Protein Receptor ◽  
Root Hair Growth ◽  
Multicellular Organisms ◽  
Ta Proteins

SolubleN-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) proteins are key players in cellular trafficking and coordinate vital cellular processes, such as cytokinesis, pathogen defense, and ion transport regulation. With few exceptions, SNAREs are tail-anchored (TA) proteins, bearing a C-terminal hydrophobic domain that is essential for their membrane integration. Recently, the Guided Entry of Tail-anchored proteins (GET) pathway was described in mammalian and yeast cells that serve as a blueprint of TA protein insertion [Schuldiner M, et al. (2008)Cell134(4):634–645; Stefanovic S, Hegde RS (2007)Cell128(6):1147–1159]. This pathway consists of six proteins, with the cytosolic ATPase GET3 chaperoning the newly synthesized TA protein posttranslationally from the ribosome to the endoplasmic reticulum (ER) membrane. Structural and biochemical insights confirmed the potential of pathway components to facilitate membrane insertion, but the physiological significance in multicellular organisms remains to be resolved. Our phylogenetic analysis of 37 GET3 orthologs from 18 different species revealed the presence of two different GET3 clades. We identified and analyzed GET pathway components inArabidopsis thalianaand found reduced root hair elongation inAtgetlines, possibly as a result of reduced SNARE biogenesis. Overexpression ofAtGET3a in a receptor knockout (KO) results in severe growth defects, suggesting presence of alternative insertion pathways while highlighting an intricate involvement for the GET pathway in cellular homeostasis of plants.

scholarly journals “Dead Cells Talking”: The Silent Form of Cell Death Is Not so Quiet

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Richard Jäger ◽  
Howard O. Fearnhead
Keyword(s):  
Cell Death ◽  
Cancer Therapy ◽  
Apoptotic Cell ◽  
Surrounding Tissue ◽  
Apoptotic Cells ◽  
Cancer Cell Proliferation ◽  
Loss Of Function ◽  
Molecular Events ◽  
Dying Cells

After more than twenty years of research, the molecular events of apoptotic cell death can be succinctly stated; different pathways, activated by diverse signals, increase the activity of proteases called caspases that rapidly and irreversibly dismantle condemned cell by cleaving specific substrates. In this time the ideas that apoptosis protects us from tumourigenesis and that cancer chemotherapy works by inducing apoptosis also emerged. Currently, apoptosis research is shifting away from the intracellular events within the dying cell to focus on the effect of apoptotic cells on surrounding tissues. This is producing counterintuitive data showing that our understanding of the role of apoptosis in tumourigenesis and cancer therapy is too simple, with some interesting and provocative implications. Here, we will consider evidence supporting the idea that dying cells signal their presence to the surrounding tissue and, in doing so, elicit repair and regeneration that compensates for any loss of function caused by cell death. We will discuss evidence suggesting that cancer cell proliferation may be driven by inappropriate or corrupted tissue-repair programmes that are initiated by signals from apoptotic cells and show how this may dramatically modify how we view the role of apoptosis in both tumourigenesis and cancer therapy.

scholarly journals Role of Cell Death in Cellular Processes During Odontogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
John Abramyan ◽  
Poongodi Geetha-Loganathan ◽  
Marie Šulcová ◽  
Marcela Buchtová
Keyword(s):  
Cell Death ◽  
Tooth Development ◽  
Apoptotic Cell ◽  
Tooth Germ ◽  
Oral Epithelium ◽  
Special Focus ◽  
Apoptotic Cells ◽  
Molecular Signaling ◽  
Apoptotic Pathway ◽  
Cellular Processes

The development of a tooth germ in a precise size, shape, and position in the jaw, involves meticulous regulation of cell proliferation and cell death. Apoptosis, as the most common type of programmed cell death during embryonic development, plays a number of key roles during odontogenesis, ranging from the budding of the oral epithelium during tooth initiation, to later tooth germ morphogenesis and removal of enamel knot signaling center. Here, we summarize recent knowledge about the distribution and function of apoptotic cells during odontogenesis in several vertebrate lineages, with a special focus on amniotes (mammals and reptiles). We discuss the regulatory roles that apoptosis plays on various cellular processes during odontogenesis. We also review apoptosis-associated molecular signaling during tooth development, including its relationship with the autophagic pathway. Lastly, we cover apoptotic pathway disruption, and alterations in apoptotic cell distribution in transgenic mouse models. These studies foster a deeper understanding how apoptotic cells affect cellular processes during normal odontogenesis, and how they contribute to dental disorders, which could lead to new avenues of treatment in the future.

Sign in / Sign up

Export Citation Format

Share Document